Objectives:To investigate the effect of the aqueous extract of Phyllanthus niruri (Aq.E.PN) against doxorubicin (Dox)-induced myocardial toxicity in rats.Materials and Methods:Cardiotoxicity was produced by Dox administration (15 mg/kg for 2 weeks). Aq.E PN (200 mg/kg, orally) was administered as pretreatment for 2 weeks alternated with Dox for the next 2 weeks. The general observations, mortality, histopathology, biomarker enzymes like lactate dehydrogenase (LDH), creatinine phosphokinase (CPK) and alkaline phosphatase, diagnostic enzyme markers like aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and antioxidants such as glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) were monitored after 3 weeks of the last dose.Results:Pretreatment with the Aq.E.PN significantly (P < 0.01) protected the myocardium from the toxic effects of Dox by reducing the elevated level of biomarker and diagnostic enzymes like LDH, CPK, AST and ALT to the normal levels. Aq.E PN increased the GSH, SOD and CAT levels and decreased the MDA levels in cardiac tissue. Administration of Dox caused cardiomyopathy associated with an antioxidant deficiency.Conclusion:These results suggest a cardioprotective effect of P. niruri due to its antioxidant properties.